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P5.074 Immune Activation After Stimulation with Cryptococcus Neoformans Antigens Pre and Post ART Initiation in HIV-1 Positive Ugandans
  1. R N Sanya1,
  2. D Chatterjea2,
  3. A Akampurrira3,
  4. P Naluyima1,
  5. D B Meya4,
  6. J H Rowe5,
  7. F Cham1,
  8. D R Boulware5
  1. 1Makerere university walter reed project, Kampala, Uganda
  2. 2Macalester college, St. Paul, MN, United States
  3. 3Makerere university medical school, Kampala, Uganda
  4. 4Infectious diseases institute, Kampala, Uganda
  5. 5University of Minnesota, Minneapolis, MN, United States

Abstract

Background Cryptococcus meningitis immune reconstitution inflammatory syndrome (CM-IRIS) is a medical condition that complicates recovery from immunodeficiency as a result of anti retroviral therapy (ART) in patients living with Human Immunodeficiency Virus type 1 (HIV-1) in the sub Sahara Africa region.

Methods This study investigated CD4 T cell immune activation based on intracellular IFN-γ and Ki-67 expression, after ex-vivo cryptococcal antigen stimulation of whole blood samples taken from HIV-1 positive adult patients infected with or without cryptococcal meningitis, initiated on ART.

Results In the CM positive group at pre-ART visit; stimulation with C.neoformans crude cell wall (CW) induced a significant increase in CD4 IFN-γ production (p < 0.05****), as compared to C.neoformans glucuronoxylomannan (GXM) polysaccharide antigen (p < 0.05*), whilst C.neoformans mannoprotein (MP) stimulation failed to induce greater than baseline IFN-γ expression. The effector memory T cell subset was the major contributor to the IFN-γ elevation exhibited in CW stimulated samples. Interestingly, T cell responses to CW were found to be significantly higher in the CM positive group compared to the CM negative group (p < 0.05*). Furthermore, stimulation with CW and GXM exhibited higher frequency of terminally differentiated effector memory T cells (TDEMS) compared to either negative control or MP stimulation.

Conclusion Immune activation of CD4 T cells can be achieved by C.neoformans CW rather than purified MP antigen, by inducing the effector memory subset to produce IFN-γ.

  • Cryptococcus meningitis
  • HIV antiretroviral therapy (ART)
  • immune reconstitution inflammatory syndrome (IRIS)

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