# ROLE OF T CELLS IN IMMUNITY TO CRYPTOCOCCOSIS

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA · 1987 · $152,353

## Abstract

Cryptococcosis is an often times fatal disease caused by a yeast-like
organism, Cryptococcus neoformans.  Patients with cryptococcosis frequently
have high levels of cryptococcal antigen in their body fluids, and antigen
levels directly correlate with the severity of disease.  Using a murine
model we have documented that animals with large numbers of cryptococci in
their tissues have high cryptococcal antigen levels in their sera and
minimal delayed-type hypersensitivity (DTH) responses to cryptococcal
antigen.  Furthermore, if cryptococcal antigen is injected into mice at
concentrations similar to those found in human systemic cryptococcosis, a
complex series of suppressor cells and factors is induced which
specifically suppresses the DTH response and the T cells responsible for in
vitro growth inhibition of cryptococci.  Two sources of cryptococcal
antigen have been shown to induce suppression.  One is an in vitro prepared
cryptococcal culture filtrate antigen (CneF), and the other is serum from
C. neoformans infected mice having a high cryptococcal antigen titer.  We
feel there is now a sufficient understanding of the mechanisms which
down-regulate the cryptococcal cell-mediated immune response, i.e. DTH, to
achieve the following proposed specific aims.  The first goal of these
proposed studies is to determine the effects on clearance of C. neoformans
from organs after mice have been suppressed by injecting tolerizing doses
of CneF or cryptococcal specific first- (Tsl) or second-order (Ts2)
suppressor cells.  Furthermore, clearance of Listeria monocytogenes in mice
treated with suppressive doses of CneF will be monitored to assess whether
or not nonspecific effects on clearance are induced by CneF.  The second
objective in these studies is to establish which component(s) of the
cryptococcal antigen is responsible for induction of suppression.  This
will be achieved by fractionating the antigen by conventional methods, and
testing the antigen fractions for suppressive capabilities.  And, third, we
will assess changes occurring at the cellular level in lymph nodes and
spleens during the induction of Tsl cells in contrast to changes occurring
during the induction of DTH.  Parameters to be monitored will be levels of
Ia antigens on lymphoid cells, IL-1 and IL-2 production, and IL-2 receptors
on cells.  A greater understanding of the effects of suppression and the
parameters involved in the induction of suppression will provide the
rationale for future investigations on effective control of the protective
immune mechanisms.

## Key facts

- **NIH application ID:** 3126370
- **Project number:** 5R01AI015716-08
- **Recipient organization:** UNIVERSITY OF OKLAHOMA
- **SAM.gov UEI:** EVTSTTLCEWS5
- **Principal Investigator:** JUNEANN W MURPHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $152,353
- **Award type:** 5
- **Project period:** 1980-04-01 → 1989-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126370

## Citation

> US National Institutes of Health, RePORTER application 3126370, ROLE OF T CELLS IN IMMUNITY TO CRYPTOCOCCOSIS (5R01AI015716-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126370. Licensed CC0.

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