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.