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 D Estes, Robert A Seder, Susan L Moir, Jason M Brenchley

Research output: Contribution to journalArticle

39 Scopus citations

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 SIVuninfected 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)5803-12
Number of pages10
JournalBlood
Volume118
Issue number22
DOIs
StatePublished - Nov 24 2011
Externally publishedYes

Keywords

  • Animals
  • B-Lymphocytes/drug effects
  • CD4-Positive T-Lymphocytes/immunology
  • Immunization, Secondary
  • Leishmania major/immunology
  • Leishmaniasis Vaccines/administration & dosage
  • Leishmaniasis, Cutaneous/prevention & control
  • Lymph Nodes/immunology
  • Lymphocyte Activation/drug effects
  • Macaca mulatta/immunology
  • Simian Acquired Immunodeficiency Syndrome/immunology
  • Simian Immunodeficiency Virus/immunology
  • T-Lymphocytes/drug effects
  • Vaccination/methods

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Intramural

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    Klatt, N. R., Vinton, C. L., Lynch, R. M., Canary, L. A., Ho, J., Darrah, P. A., Estes, J. D., Seder, R. A., Moir, S. L., & 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), 5803-12. https://doi.org/10.1182/blood-2011-07-365874