SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Nichole R. Klatt, Carol L. Vinton, Rebecca M. Lynch, Lauren A. Canary, Jason Ho, Patricia A. Darrah, Jacob Estes, Robert A. Seder, Susan L. Moir, Jason M. Brenchley

Research output: Contribution to journalArticle

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Abstract

HIV infection is characterized by immune system dysregulation, including depletion of CD4 + T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIV-uninfected animals induced high frequencies of polyfunctional MML-specific CD4 +T cells. However, in SIV-infected animals, CD4 + T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.

Original languageEnglish (US)
Pages (from-to)5803-5812
Number of pages10
JournalBlood
Volume118
Issue number22
DOIs
StatePublished - Nov 24 2011
Externally publishedYes

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Leishmania major
T-cells
Macaca mulatta
Vaccination
B-Lymphocytes
Cells
T-Lymphocytes
Infection
Animals
Helper-Inducer T-Lymphocytes
Antigens
Data storage equipment
Polyproteins
Antibodies
Immune system
Opportunistic Infections
Immunoglobulin A
HIV Infections
Immune System
Vaccines

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Klatt, N. R., Vinton, C. L., Lynch, R. M., Canary, L. A., Ho, J., Darrah, P. A., ... Brenchley, J. M. (2011). SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination. Blood, 118(22), 5803-5812. https://doi.org/10.1182/blood-2011-07-365874

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination. / Klatt, Nichole R.; Vinton, Carol L.; Lynch, Rebecca M.; Canary, Lauren A.; Ho, Jason; Darrah, Patricia A.; Estes, Jacob; Seder, Robert A.; Moir, Susan L.; Brenchley, Jason M.

In: Blood, Vol. 118, No. 22, 24.11.2011, p. 5803-5812.

Research output: Contribution to journalArticle

Klatt, NR, Vinton, CL, Lynch, RM, Canary, LA, Ho, J, Darrah, PA, Estes, J, Seder, RA, Moir, SL & Brenchley, JM 2011, 'SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination', Blood, vol. 118, no. 22, pp. 5803-5812. https://doi.org/10.1182/blood-2011-07-365874
Klatt, Nichole R. ; Vinton, Carol L. ; Lynch, Rebecca M. ; Canary, Lauren A. ; Ho, Jason ; Darrah, Patricia A. ; Estes, Jacob ; Seder, Robert A. ; Moir, Susan L. ; Brenchley, Jason M. / SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination. In: Blood. 2011 ; Vol. 118, No. 22. pp. 5803-5812.
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abstract = "HIV infection is characterized by immune system dysregulation, including depletion of CD4 + T cells, immune activation, and abnormal B- and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIV-uninfected animals induced high frequencies of polyfunctional MML-specific CD4 +T cells. However, in SIV-infected animals, CD4 + T-cell functionality decreased after both neo (P = .0025) and recall (P = .0080) MML vaccination. Furthermore, after SIV infection, the frequency of MML-specific antibody-secreting classic memory B cells was decreased compared with vaccinated, SIV-uninfected animals. Specifically, antibody-secreting classic memory B cells that produced IgA in response to either neo (P = .0221) or recall (P = .0356) MML vaccinations were decreased. Furthermore, we found that T-follicular helper cells, which are essential for priming B cells, are preferentially infected with SIV. These data indicate that SIV infection results in dysfunctional T-cell responses to neo and recall vaccinations, and direct SIV infection of T-follicular helper cells, both of which probably contribute to deficient B-cell responses and, presumably, susceptibility to certain opportunistic infections.",
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AU - Ho, Jason

AU - Darrah, Patricia A.

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